Circulating Th2 memory cells in IgG4-related disease are restricted to a defined subset of subjects with atopy.

IgG4-related disease (IgG4-RD) is characterized by a lymphoplasmacytic infiltrate composed of IgG4(+) plasma cells, tumefactive lesions, obliterative phlebitis, and mild to moderate eosinophilia. It has been suggested that IgG4-RD is characterized by allergic manifestations and is potentially driven by enhanced T-helper type 2 (Th2) responses. We aimed to investigate the potential contribution of atopy to enhanced Th2 responses in IgG4-RD. Peripheral blood mononuclear cells from 39 patients were isolated and subjected to in vitro mitogenic stimulation with PMA and ionomycin. Following stimulation, gated CD3(+) CD4(+) T cells were analyzed for production of the Th2 cytokines IL-4, IL-5, and IL-13. Among the 39 patients analyzed, only the 18 patients who had a history of atopy showed increases in circulating Th2 memory cells. Our results indicate that Th2 responses that have been reported in IgG4-RD may result from concomitant atopic manifestations in disease subjects.

Differential activity of cathepsin L in human placenta at two different stages of gestation.

The implantation of blastocyst depends on the invasiveness of the syncytiotrophoblast, which penetrates the maternal decidua to establish the placenta. Cathepsin L, a lysosomal cysteine protease over-expressed in a variety of human malignancies, has been implicated in tumour invasion and metastasis. Specific inhibitors of cathepsin L inhibit the invasion of amnion by murine tumour cells. Previous studies have revealed that tumour and trophoblast invasiveness are mediated by shared factors, like metalloproteinases and laminin. Several proteases closely related to cathepsin L have recently been reported in the placentae of different species. In the present study, we demonstrate the expression of cathepsin L in human placenta by immunohistochemical analysis and RT-PCR followed by Southern hybridization. The activity of cathepsin L against the synthetic dipeptidyl substrate, Cbz-Phe-Arg-N-Methylcoumarin, was assayed. E-64, a specific inhibitor of cathepsin L was used to confirm that the enzyme activity being measured was due to cathepsin L. We observed the specific activity of cathepsin L in first trimester placenta to be significantly higher as compared to the term placenta. However, the levels of placental cathepsin L mRNA were comparable at these two stages of gestation. The increased enzymatic activity of cathepsin L in the invasive phase of placentation taken together with its previously established role in tumour invasion and metastasis indicates the involvement of this protease in trophoblast invasion.